The application of a hollow waveguide (HW) was investigated as a gas cell for analytical infrared analysis. The analysis was the measurement of carbon monoxide (CO) and nitric oxide (NO) in sidestream cigarette smoke. An FT-IR analysis system was setup with a 3m multi-pass gas cell and a 55cm by 2mm i.d. Ag/AgI coated HW in tandem with individual CO and NO gas analyzers. The HW demonstrated response times an order of magnitude less than the larger volume multi-pass gas cell and slightly faster than the single analyte gas analyzer. Furthermore, it has been demonstrated that the HW provides up to approx. 60% greater sensitivity on a per meter optical path basis than the multi-pass gas cell of the analytes investigated due to increased optical efficiency maximizing the light concentration within the gaseous sample volume. Simulations in 3-D showed the sensitivity could theoretically improve by more than an order of magnitude if the IR beam was coupled more efficiently into the waveguide. Both FT-IR configurations gave statistically equivalent results for CO to the independent analyzers. With the HW increased temporal resolution, inter-puff measurements comparable to the gas analyzer were achieved at a lower spectral resolution. The HW optical configuration was modeled for ray tracing in MATLAB. Simulations in 2-D and 3-D were accomplished. The simulations show a major drawback to HW optimization is the coupling of the infrared beam into the waveguide. As demonstrated in a 3-D simulation, approximately 97% of the rays are rejected when an off-axis parabolic mirror with 25.4mm focal length is used to focus the IR beam into the 2mm i.d. waveguide. Repeating the simulation with longer focal length mirrors showed improved in IR coupling into the waveguide from 3% to 85%. Simulations applying a compound parabolic concentrator show comparable performance to the traditional design of two OAP mirrors to collect rays from the HW and focus onto the detector, but in a much smaller configuration. The simulation routines can be used to further improve the design of this and other optical sensing systems and enhanced by incorporating a spectral component to the simulation.

Thesis (Ph. D.)--Illinois State University, 1980. / Title from title page screen, viewed Feb. 17, 2005. Dissertation Committee: Herman Brockman (chair), Arlan Richardson, David Weber, Alan Katz, Brian Wilkinson. Includes bibliographical references (leaves 150-166) and abstract. Also available in print.

The thesis topic bears the name: "Aspect of smoking among students of high medical schools". Smoking is one the most often appearing drug addictions nowadays in Europe. With reference to the World Health Organization, there are 1.3 billion of smoking people in the world today whereas consequences of smoking kill approximately 4.8 million of people every year, which are 560 people each hour. If the current trend continues, then in the current pace 10 million of people will die of the consequences of cigarette smoking during the year of 2020. Smoking invokes an enormous addiction to nicotine which bears itself considerable economic, social and health problems. There were some students from 1st and 4th grade of the present form of studies of all high medical schools selected. Those were students particularly from the schools: SZŠ and VOŠZ České Budějovice, SOŠZ and SOU Český Krumlov, SZŠ Jindřichův Hradec, SZŠ Tábor and SZŠ Písek. In total, 591 of students were responded whereas most of them were girls (87%). The average age of the responded ones was 17 years. The thesis consists of theoretical and empirical parts. The theoretical part deals with history of cigarette smoking, a definition of drug addiction, chemical composition of cigarette smoke and malignity of individual toxic elements. Further, there is a chapter concerning problem issues of electronic cigarette smoking in the theoretical part. In the conclusion of this part of the thesis, there are some statistical data referring to cigarette smoking stated. There are some findings of quite a few of authors dealing with problem issues of cigarette smoking and addiction to nicotine summarized here. The empirical part consists of findings from my own research analysis which was done with the intention to map the prevalence of smoking among future health workers and their opinion to cigarette smoking among healthcare staff and people preparing for their healthcare career. There are also the respondents' opinions and attitudes included. The aim of the thesis was: 1.: To find the prevalence of smoking of 1st and 4th grade of high medical schools students. 2.: To find what influence the respondents' surroundings have on the fact of their smoking. 3.: To find what attitude high medical school students have to healthcare staff smoking cigarettes. To reach the above mentioned aims, there were three hypotheses determined: H1: There is a statistically significant difference existing in the prevalence of smoking at 1st and 4th grade of high medical school students. H2: There is a statistically significant difference existing in the prevalence of cigarette smoking among students coming from families where at least one member smokes. H3: There are statistically significant differences in the attitude of 1st and 4th grade students to cigarette smoking among healthcare workers. To prove or disprove the mentioned hypotheses there is a method of quantitative research selected. A questionnaire was used to collect the data. The questionnaires including 23 questions were distributed among 591 students of high medical schools of the South Bohemia Region. Their rate of return was 85%. The collected data were processed in the form of transparent graphs and the hypotheses were statistically tested. Pursuant to the evaluation of respondents' answers including the statistical data testing were proved by the hypothesis which presumed that there were statistically significant differences in the prevalence of cigarette smoking 1st and 4th grade students. The difference really exists that the 4th grade students smoke more often. It is interesting that the most considerable difference is between the schools of SZŠ and VOŠZ České Budějovice. On the contrary, the percentage of smoking students of SOŠZ Český Krumlov in the 1st grade is considerably high. Hypothesis no. 2 was statistically proved as well. There is a real significant difference exist

Em meio ao declínio do consumo de cigarros devido ao aumento das campanhas restritivas e a crescente consciência pública dos riscos associados à saúde dos fumantes, as indústrias de cigarros se deparam com o constante desafio de desenvolver novas tecnologias de fabricação e materiais que minimizem os efeitos da fumaça de cigarros sobre a saúde dos consumidores. O sabor e a composição da fumaça ingerida pelo fumante durante o ato de fumar dependem fundamentalmente da combinação do design do cigarro e do blend de fumo utilizado. O interesse na realização desta pesquisa foi avaliar a influência da densidade do filtro de cigarros na redução dos teores dos principais constituintes da fumaça. Para a realização do estudo, protótipos de cigarro foram fabricados em escala industrial, utilizando o mesmo blend de fumo e demais parâmetros de design do cigarro, apenas variando a especificação do denier do acetato de celulose utilizado na fabricação do filtro. O desempenho dos filtros como material filtrante da fumaça foi avaliado em termos da queda de pressão e das propriedades da fibra do cabo de acetato. E, utilizando métodos padronizados, os protótipos de cigarro foram fumados em máquina de fumar e a composição dos teores de alcatrão, nicotina e monóxido de carbono foi determinada para a avaliação da capacidade de retenção dos filtros de cigarro fabricados com diferentes densidades. Os resultados mostram que a utilização de cabos de acetato com menor denier por filamento nos filtros de cigarro apresenta grande desempenho na redução dos constituintes da fase particulada da fumaça, como o alcatrão e a nicotina, porém não apresenta efeito na redução do monóxido de carbono, substância volátil presente na fase vapor da fumaça. No entanto, cabos de acetato com menor espessura dos filamentos somente podem ser utilizados em filtros de cigarro se combinados com outros parâmetros de design de cigarro a fim de não apresentar prejuízo na aceitação do produto junto aos consumidores, devido ao aumento no esforço para a realização da tragada. / In the middle of the cigarette consumption decline caused by the increase of restrictive advertising campaigns and smokers’ health risk public awareness, tobacco industries now encounter the permanent challenge of developing materials and new manufacturing technologies to minimize cigarette smoke effects in regards to consumers’ health. The taste and formulation of the smoke absorbed in the smoking activity crucially depend on the combination between cigarette design and tobacco blend. The aim in this research was to evaluate the influence of cigarette filter density to reduce the level of smoke main constituents. In order to conduct the study, cigarette prototypes were manufactured at industrial proportion, using the same tobacco blend and respective cigarette design parameters, but only varying the denier specification of the cellulose acetate filter tow used to produce the filter. The performance of filters as smoke-filtering materials were evaluated in terms of pressure drop and filter tow fiber properties. And, according standardized methods, cigarette prototypes were smoked in smoking machines, and the composition of tar, nicotine and carbon monoxide levels was determined to evaluate the retention capacity of the cigarette filters manufactured with different densities. Results show that the use of filter tows with low denier per filament in cigarette filters increases smoke particulate phase components removal efficiency, such as tar and nicotine, but it does not present effects to reduce carbon monoxide, volatile substance that exists in the smoke vapor phase. However, filter tows with of filaments can only be used in cigarette filters if combined with other design parameters in order to avoid damage in the product acceptance by consumers due to the increase of effort in the cigarette puff.

Em meio ao declínio do consumo de cigarros devido ao aumento das campanhas restritivas e a crescente consciência pública dos riscos associados à saúde dos fumantes, as indústrias de cigarros se deparam com o constante desafio de desenvolver novas tecnologias de fabricação e materiais que minimizem os efeitos da fumaça de cigarros sobre a saúde dos consumidores. O sabor e a composição da fumaça ingerida pelo fumante durante o ato de fumar dependem fundamentalmente da combinação do design do cigarro e do blend de fumo utilizado. O interesse na realização desta pesquisa foi avaliar a influência da densidade do filtro de cigarros na redução dos teores dos principais constituintes da fumaça. Para a realização do estudo, protótipos de cigarro foram fabricados em escala industrial, utilizando o mesmo blend de fumo e demais parâmetros de design do cigarro, apenas variando a especificação do denier do acetato de celulose utilizado na fabricação do filtro. O desempenho dos filtros como material filtrante da fumaça foi avaliado em termos da queda de pressão e das propriedades da fibra do cabo de acetato. E, utilizando métodos padronizados, os protótipos de cigarro foram fumados em máquina de fumar e a composição dos teores de alcatrão, nicotina e monóxido de carbono foi determinada para a avaliação da capacidade de retenção dos filtros de cigarro fabricados com diferentes densidades. Os resultados mostram que a utilização de cabos de acetato com menor denier por filamento nos filtros de cigarro apresenta grande desempenho na redução dos constituintes da fase particulada da fumaça, como o alcatrão e a nicotina, porém não apresenta efeito na redução do monóxido de carbono, substância volátil presente na fase vapor da fumaça. No entanto, cabos de acetato com menor espessura dos filamentos somente podem ser utilizados em filtros de cigarro se combinados com outros parâmetros de design de cigarro a fim de não apresentar prejuízo na aceitação do produto junto aos consumidores, devido ao aumento no esforço para a realização da tragada. / In the middle of the cigarette consumption decline caused by the increase of restrictive advertising campaigns and smokers’ health risk public awareness, tobacco industries now encounter the permanent challenge of developing materials and new manufacturing technologies to minimize cigarette smoke effects in regards to consumers’ health. The taste and formulation of the smoke absorbed in the smoking activity crucially depend on the combination between cigarette design and tobacco blend. The aim in this research was to evaluate the influence of cigarette filter density to reduce the level of smoke main constituents. In order to conduct the study, cigarette prototypes were manufactured at industrial proportion, using the same tobacco blend and respective cigarette design parameters, but only varying the denier specification of the cellulose acetate filter tow used to produce the filter. The performance of filters as smoke-filtering materials were evaluated in terms of pressure drop and filter tow fiber properties. And, according standardized methods, cigarette prototypes were smoked in smoking machines, and the composition of tar, nicotine and carbon monoxide levels was determined to evaluate the retention capacity of the cigarette filters manufactured with different densities. Results show that the use of filter tows with low denier per filament in cigarette filters increases smoke particulate phase components removal efficiency, such as tar and nicotine, but it does not present effects to reduce carbon monoxide, volatile substance that exists in the smoke vapor phase. However, filter tows with of filaments can only be used in cigarette filters if combined with other design parameters in order to avoid damage in the product acceptance by consumers due to the increase of effort in the cigarette puff.

Le tabagisme actif par la mère expose le fœtus en développement à des agents qui peuvent traverser la barrière placentaire et interférer avec les fonctions placentaires. Un large éventail de fonctions immunologiques, pourrait être compromises. Dans cette étude, nous avons évalué l'effet de l'extrait de la fumée de cigarette (CSE) sur les macrophages isolés à partir de placentas humains (pMφs), qui sont les principaux partenaires de l'immunité de fœto-maternelle innée. J’ai pu montrer que le CSE inhibe la formation des cellules géantes multinucléées (MGC). Cette propriété du CSE est spécifique aux macrophages car la fusion des macrophages dérivés des monocytes est inhibée lors de la formation de granulomes in vitro. J’ai également étudié l'absorption de particules et la production de cytokines par pMφs exposés au CSE. Le CSE a inhibé l'absorption des particules de zymosan, mais pas celle du zymosan opsonisé, ce qui suggère qu’il interfère avec les récepteurs phagocytaires et non phagocytaires. Le CSE augmente la libération de TNF et d'IL-33, et une diminue celle de l'IL-10, ce qui montre que l'équilibre entre les cytokines est affecté par le CSE. En outre, l’expression des métalloprotéinases telles que les MMP-1, MMP-10 et MMP-12, connues pour être impliquées dans le remodelage des tissus et la fusion des macrophages est dérégulée. Enfin, j’ai montré que la nicotine, l'un des principaux composés de tabac, n'a pas affecté les propriétés fonctionnelles des pMφs. / Active smoking by the mother exposes the developing fetus to agents that can cross the placental barrier and interfere with placental functions. A wide range of immunological functions, including innate and adaptive immune responses, might be impaired. In this study, we assessed the effect of cigarette smoke extract (CSE) on macrophages isolated from human placentas (pMφs), which are major partners of innate feto-maternal immunity. I showed that CSE significantly inhibited the formation of multinucleated giant cells (MGCs). This property of CSE is specific to macrophages because the fusion of monocyte-derived macrophages is inhibited during the in vitro formation of granulomas. I also investigated particle uptake and cytokine production by pMφs exposed to CSE. CSE inhibited the uptake of zymosan, but not that of opsonized zymosan, suggesting that it interferes with phagocytic receptors, not with the phagocytic machinery of pMφs. CSE increased the release of Tumor Necrosis Factor and interleukin-33, and decreased that of interleukin-10, demonstrating that the balance between inflammatory and anti-inflammatory cytokines is affected by CSE. Furthermore, CSE enhanced the expression of metalloproteinase (MMPs) genes such as MMP-1, MMP-10 and MMP-12, known to be involved in tissue remodeling including macrophage fusion. Finally, I showed that nicotine, one of the major compounds of tobacco, did not affect the functional properties of pMφs.

La bronchopneumopathie chronique obstructive (BPCO) est une maladie caractérisée par une réaction inflammatoire intense avec une destruction du parenchyme pulmonaire et une perte d’élasticité du poumon conduisant à une obstruction quasi-irréversible des voies aériennes. L’utilisation du tabac est le principal facteur de risque de cette maladie. La fumée de cigarette active les cellules épithéliales et les macrophages résidents en libérant des protéases et des chimiokines. Ces phénomènes sont responsables de l’infiltration de cellules inflammatoires dans le poumon, telles que les neutrophiles, les macrophages et les lymphocytes. Ces cellules libèrent des enzymes protéolytiques capables de dégrader les composants de la matrice extracellulaire. Parmi ces protéases, l’élastase du neutrophile (NE) semble stimuler la sécrétion de cytokines, participant ainsi à une inflammation chronique. De fortes évidences montrent que des infections bactériennes récurrentes contribuent à ce processus inflammatoire et par conséquent à l’aggravation de la BPCO. A partir de ces observations, nous nous sommes intéressés aux événements précoces du développement de la BPCO associés à une infection bactérienne récurrente. Dans un premier temps, nous avons montré que l’association d’un extrait de fumée de cigarette à de faibles doses de LPS est capable d’augmenter de façon synergique la libération des chimiokines par les cellules épithéliales alvéolaires. Ce phénomène implique l’activation des voies de signalisation MAP kinase ERK1/2 et JAK/STAT. Nous avons mis en évidence que l’inhibiteur de la phosphodiestérase 4, le roflumilast N-oxide, empêche la sécrétion de ces cytokines inactivant ainsi les voies JAK/STAT et ERK1/2. Dans un deuxième temps, nous avons démontré que la NE peut conduire à la libération de chimiokines par des cellules épithéliales alvéolaires en activant la voie de signalisation p38 et que le roflumilast N-oxide diminue le taux de ces chimiokines. Une approche in vitro sur un modèle de cellules épithéliales alvéolaires a permis de démontrer l’effet synergique du CSE associé au LPS sur la libération de cytokines et sur l’activation des voies de signalisation. Cet effet pourrait être responsable de la progression et de l’exacerbation de la BPCO. Notre étude montre aussi les effets du roflumilast sur la libération de cytokines induites par la NE ou par le CSE/LPS. Ces résultats mettent en lumière d’autres mécanismes par lesquels le roflumilast N-oxide exerce son effet anti-inflammatoire dans la BPCO. / Chronic obstructive pulmonary disease (COPD) is a pathology characterized by an abnormal inflammatory response and associated with a destruction of lung parenchyma and loss of lung elasticity, leading to an airway limitation not fully reversible. Tobacco smoking continues to be a major cause of COPD. Cigarette smoke activates epithelial cells and resident macrophages by releasing proteases and chemokines. This phenomenon is responsible of the migration of inflammatory cells in the lung tissue such as neutrophils, macrophages and lymphocytes. These cells are able to release proteolytic enzymes leading to the degradation of components of the extracellular matrix. Among these proteases, neutrophil elastase (NE) seems to stimulate the secretion of cytokines involved in chronic inflammation. Strong evidence shows that recurrent bacterial infections contribute to the inflammatory process and consequently to the worsening of COPD. Based on these observations, we studied the early events in the development of COPD associated with recurrent bacterial infection. Initially we showed that the combination of a cigarette smoke extract associated with low doses of LPS is able to synergistically increase the release of chemokines, by alveolar epithelial cells through the activation of MAP kinase signaling pathways ERK1/2 and JAK/STAT. We also demonstrated that the phosphodiesterase 4 inhibitor, roflumilast N-oxide (RNO) inhibits the secretion of these cytokines, thereby inactivating pathways JAK/STAT and ERK1/2. Moreover, we have demonstrated that neutrophil elastase (NE) can lead to the release of chemokines by alveolar epithelial cells by activating the p38 signaling pathway. Moreover the treatment of the cells with roflumilast N-oxide significantly reduces the production of these chemokines. This in vitro model demonstrates the synergistic effect of CSE associated with LPS on the release of cytokines and activation of signaling pathways. This effect could be responsible for the progression and exacerbation of COPD. Our study also shows the effect of RNO on the release of cytokines induced by NE or by the combination CSE/LPS. These results highlight other mechanisms by which Roflumilast N-oxide exerts its anti-inflammatory effect in COPD

La fumée de cigarette peut endommager plusieurs organes de notre organisme, causant des maladies chroniques sévères et divers types de cancers. Elle interagit notamment avec les enzymes de métabolisme des médicaments de phase I et II, et contribue ainsi à la perturbation de la pharmacocinétique de divers médicaments chez les fumeurs. Les transporteurs membranaires sont des acteurs majeurs de l'absorption, la distribution et l'élimination de médicaments, et certains sont impliqués dans les interactions médicamenteuses. De plus, ils assurent le flux des molécules endogènes physiologiques vitales, et l'élimination de divers xénobiotiques toxiques non seulement chez les mammifères mais aussi chez les êtres unicellulaires, comme les levures. Ces transporteurs sont des cibles potentielles de la fumée de cigarette. D’où l'importance d'étudier l'interaction de la fumée de cigarette et de ses composés avec les transporteurs membranaires. Nos résultats démontrent que le condensat de fumée de cigarette (CSC) modifie l'activité fonctionnelle et/ou l'expression de plusieurs transporteurs hépatiques et rénaux in vitro dans des modèles cellulaires hépatiques et/ou non-hépatiques, notamment les OATPs (organic anion transporting polypeptide), l'OCT1 (organic cation transporter 1), la BCRP (breast cancer resistance protein) et l'OAT3 (organic anion transporter 3). Une implication remarquable du récepteur Ah (AhR) est mise en évidence dans la régulation de l'expression de certains transporteurs comme la MRP4 (multidrug resistance-associated protein), la BCRP, l'OAT2 et l'OCT1 dans des cellules HepaRG exposées au CSC. De plus, chez la levure Saccharomyces cerevisiae, le CSC inhibe l'activité d'efflux notamment des transporteurs de la rhodamine 123 et de la caféine, et induit, après trois heures, leur expression avec d'autres gènes qui sont aussi impliqués dans la résistance aux xénobiotiques comme les transporteurs de la membrane plasmique le Pdr5, le Snq2, le Pdr10, le Pdr15 et le Tpo1. Enfin, un effet inhibiteur remarquable des amines aromatiques hétérocycliques (AAH) est mis en évidence in vitro, notamment celui de Trp-P-1 et de Trp-P2 sur l'activité des transporteurs OCT1 et OCT2. De plus, les données in silico suggèrent que des descripteurs moléculaires des AAH comme l'AMW (average molecular weight), la qnmax (maximum negative charge) et le SPP (submolecular molarity parameter), sont des paramètres cruciaux de l'inhibition commune des OCT1, OCT2 et OCT3 par les AAH. Le CSC est donc un modulateur bifonctionnel, qui peut intervenir dans la régulation de l'activité et de l'expression des transporteurs membranaires hépatiques et rénaux, ainsi que ceux chez la levure. De telles interactions peuvent contribuer à l'altération de la pharmacocinétique des médicaments et des composés endogènes chez les fumeurs, d’où l'évaluation de l'exposition hépatique et rénale au CSC demeure indispensable. / Cigarette smoke can damage every part of our body, causing severe chronic diseases and various types of cancers. It also interacts with drug metabolizing enzymes of phase I and II, and thus contributes to pharmacokinetics disruption of various drugs in smokers. Membrane drug transporters are major actors involved in drugs absorption, distribution and elimination, and some are involved in drug-drug interactions. In addition, membrane drug transporters ensure the flow of vital physiological endogenous molecules, and the elimination of various toxic xenobiotics, not only in mammals but also in unicellular organisms, especially in yeasts. Therefore, this indicates the importance of studying the interaction of cigarette smoke and its contained chemicals with drug transporters. Our results demonstrate that cigarette smoke condensate (CSC) modifies the functional activity and / or expression of several hepatic and renal transporters in vitro in hepatic and / or non-hepatic cellular models, including OATPs (organic anion transporting polypeptide), OCT1 (organic cation transporter 1), BCRP (breast cancer resistance protein) and OAT3 (organic anion transporter 3). A remarkable implication of Ah receptor (AhR) was also demonstrated in MRP4 (multidrug resistance-associated protein), BCRP, OAT2 and OCT1 expression regulation in HepaRG cells exposed to CSC. In addition, in Saccharomyces cerevisiae, CSC inhibits the efflux activity of at least the rhodamine 123 and caffeine transporters, and induces, after three hours, their expression and that of others involved in xenobiotic resistance such as plasma membrane transporters Pdr5, Snq2, Pdr10, Pdr15 and Tpo1. Finally, a remarkable inhibitory effect of heterocyclic aromatic amines (HAA) is demonstrated in vitro, in particular that of Trp-P-1 and Trp-P-2 on the activity of OCT1 and OCT2. In addition, in silico data suggest that molecular descriptors of HAA such as AMW (average molecular weight), qnmax (maximum negative charge) and SPP (submolecular molarity parameter), may represent crucial parameters for common inhibition of OCT1, OCT2 and OCT3 transporters by HAA. Thus, CSC acts as bifunctional modulator, which can regulate activity and expression of hepatic and renal drug transporters as well as some membrane transporters in yeasts. Such interactions may contribute to the alteration of the pharmacokinetics of drugs and endogenous compounds in smokers, hence the evaluation of hepatic and renal exposure to CSC remains essential.

No description available.

No description available.